Functional and structural brain network correlates of visual hallucinations in Lewy body dementia.

Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature.

Meningococcal carriage in adolescents in the United Kingdom to inform timing of an adolescent vaccination strategy.

OBJECTIVES: Recent development of serogroup B meningococcal (MenB) vaccines highlights the importance of pharyngeal carriage data, particularly in adolescents and young adults, to inform implementation strategies. We describe current UK carriage prevalence in this high risk population and compare methods of carriage detection. METHODS: In this multisite study, pharyngeal swabs were collected on 3-4 occasions over 6-12 months, from 1040 school and university students, aged 10-25 years. Meningococcal carriage was detected by standard culture combined with seroagglutination or PCR of cultured isolates, or by direct PCR from swab. The factor H binding protein (fHBP) variants present in meningococcal isolates were determined. RESULTS: Meningococcal serogroups B and Y were most common, with carriage up to 6.5% and 5.5% respectively, increasing throughout adolescence. Identification by seroagglutination was often unreliable, and the sensitivity of direct PCR detection was 66% compared to culture combined with PCR. Of MenB isolates, 89.1% had subfamily A variants of fHBP. The acquisition rate of MenB carriage was estimated at 2.8 per 1000 person-months. CONCLUSIONS: If vaccination is to precede the adolescent rise in MenB carriage, these data suggest it should take place in early adolescence. Studies assessing vaccine impact should use molecular methods to detect carriage.

Review of diphtheria, tetanus and pertussis vaccines in clinical development.

Diphtheria, tetanus and pertussis vaccines have formed the cornerstone of childhood immunization programs for decades. Historically, these have comprised diphtheria and tetanus toxoids combined with inactivated whole-cell pertussis. More recently, advances have been made with the development of purified acellular pertussis vaccines, with improved reactogenicity profiles, and formulation with additional vaccines such as Haemophilus influenzae type b, hepatitis B virus and inactivated poliovirus. Development is currently focused on maximizing the number of vaccines that can be combined in a single formulation and strategies to provide protection against pertussis before the commencement of routine infant immunization.

Comparison of two combined vaccines against typhoid fever and hepatitis A in healthy adults.

A prospective, randomised, observer-blind, comparative study was performed in healthy adults with a new hepatitis A/typhoid combined vaccine, Viatim, and the marketed Hepatyrix vaccine. Both vaccines induced high levels of protective antibodies, but typhoid responses were higher and hepatitis A responses more rapid with Viatim compared with Hepatyrix. Both vaccines were well tolerated, no serious adverse events (SAEs) occurred, but more Viatim vaccinees had more mild or moderate local reactions (82.7%) than Hepatyrix (53.1%, p < 0.001). In this direct comparison Viatim induced more local reactions, but elicited a more rapid and higher immune response to both antigens than Hepatyrix.

Occurrence of adverse events following inadvertent administration of childhood vaccines.

As a service to healthcare professionals, Aventis Pasteur MSD UK Ltd. operates a telephone-based Vaccine Information Service, providing information on all aspects of vaccination. In the UK it is the primary means by which spontaneous adverse drug reaction reports are received by the company. It was brought to the attention of the Pharmacovigilance Department that a significant number of calls related to people seeking advice following inadvertent administration of vaccines. To inform our advice it was decided to collect details of such episodes, to enquire whether an adverse drug reaction had already occurred, and to encourage reporting of adverse drug reaction that may occur subsequently. Inadvertent vaccination during pregnancy was not included in this survey since these data were already being collected separately. During the period from 1 September 1999 to 31 August 2000 the Vaccine Information Service received 124010 enquiries. Of these, 302 (0.2%) concerned inadvertent administration of one or more vaccines (all age groups), 161 (53.2% of total inadvertent administration) of them in children (<18 years). These 161 reports involved the inadvertent administration of 221 vaccines. In six cases (3.8%) one or more adverse drug reaction were reported following the inadvertent administration. Five of these six cases involved a DTP-containing vaccine: one case where DTP was given instead of diphtheria and tetanus toxoid (DT) vaccine as a pre-school booster, one case where a fourth dose of DTP-Haemophilus influenzae type b conjugate vaccine (Hib) was given at 20 weeks of age and three cases where DTP was mixed with DTP-Hib. The sixth case involved a child given an adult dose of hepatitis B vaccine. Data are available for five of these six cases-all adverse drug reactions were non-serious and resolved without sequelae.Inadvertent administration of vaccines in childhood, although worrying for both the healthcare professionals and the parents involved, seems rarely to result in adverse reactions.